Clozapine is the most effective antipsychotic for schizophrenia treatment, a lifelong debilitating and devastating disorder. It is also the only antipsychotic with clinical practice guidelines recommending to have dosage guided by blood level measurements for optimum efficacy. Yet, clozapine remains underutilized because of its frequent blood draws for monitoring blood levels and white blood cell counts. In fact, clozapine may be one of the most underutilized evidence based treatments in mental health. Real time monitoring of efficacy and safety through therapeutic plasma ranges, and eventually monitoring for side effects (particularly white blood cell counts), will enable personalized medicine and lead to better utilization of this medication, improve treatment success rates and potentially lead to millions of dollars in decreased hospitalization and treatment costs. Lab-on-a-Chip (LOC) devices are translational microsystems that provide numerous advantages in clinical diagnostics, bringing bench top methods into the point of care. The proposed innovative research project will develop a novel and high throughput biosensor based on an arrayed electrochemical LOC, integrated with chitosan-based selective probes for real time low volume analysis of clozapine blood levels. The device will be optimized for sensitive and specific in-situ clozapine detection. We will validate the LOC with blood sample analysis in clozapine-treated patients with reference to standard laboratory means, both in a highly controlled inpatient setting for sensitivity and in an outpatient setting for selectivity. This work is the first step towards fture research proposals for the development and integration of white blood cell monitoring and elicited user requirements into the LOC. Such future devices with sample handling and automation micro-systems will allow treatment teams to do blood analysis on-site, thus improving use and acceptance, decreasing costs and revolutionizing schizophrenia treatment with clozapine. 1